Optimized DNA Vaccines

VGX Animal health has the key pieces of technology needed to rapidly develop its DNA vaccine pipeline:
		In-house expertise that allows VGX Animal Health to evaluate the gene sequences of historical, existing, as well as emerging strains of infectious agents such as viruses. Using computer modeling, VGX Animal Health is able to rapidly develop synthetic SynCon™ DNA consensus gene sequences that code for the production of the most effective immunogenic proteins possible.
		Licenses to gene expression technology that allow the targeted gene sequences to be expressed at high levels in the target animal species.
		Licenses to key manufacturing technology that allows for cost efficient manufacturing of the plasmid based DNA vaccine platform.
		License to Inovio's revolutionary gene delivery electroporation technology known as CELLECTRA®.

		Five groups of 10 mice each were immunized biweekly with 10µg of a single construct at weeks 0, 2 & 4 and then boosted at week 8 with 25µg of the relevant construct.
		Animals were then challenged with a lethal dose of a Vietnamese strain of avian H5N1 virus and assessed for survival. One hundred percent (100%) of animals who received the HA DNA vaccine survived; 80% of animals receiving the M2e-NP survived.
			Naïve Group: 10= 0% lethality by day 9. H5 Immunized Group: 100% protection at day 17. NA, M1, M2E-NP Immunized Groups: 60%, 80%, 0% protection from disease.

Additional work in pigs and ferrets has proven that this vaccine was able to protect 100% of the vaccinated animals from a virulent challenge with another strain of virus. (www.viralgenomix.com/PR_111207.html)

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VGX Animal Health, a leader in DNA vaccine design, development and delivery, announced today that the company's SynCon™ H1N1 influenza DNA vaccines achieved protective antibody responses against H1N1 swine influenza virus (A/Swine/Iowa/35233/1999) in 100% of pigs immunized with a two-dose vaccine regimen.

In this study, scientists immunized pigs with consensus H1N1 influenza DNA vaccine candidates on day 0, day 14, and day 28. Sera collected on day 28 and day 42, after two or three doses of vaccine, respectively, showed hemagglutination inhibition (HI) titers above the protection threshold in 100% of the vaccinated animals against a swine H1N1 virus previously isolated from pigs. On-going additional animal studies are testing the ability of Inovio's SynCon™ human H1N1 and swine H1N1 based vaccines to cross-protect from currently circulating human and swine H1N1 viruses as well as the new influenza A/H1N1 of swine origin.

In a similar collaborative study with scientists from the National Microbiology Laboratory of the Public Health Agency of Canada and the University of Pennsylvania, Inovio previously demonstrated that mice immunized with Inovio's SynCon™ H1N1 DNA vaccine provided 100% protection in a lethal challenge study against an unmatched H1N1 virus that caused the 1918 Spanish flu, which killed over 40 million people worldwide.

VGX Animal Health's novel SynCon™ technology enables the company to design DNA-based vaccines with the potential to protect against unmatched sub-types and strains of pathogens. Using a designer approach, VGX Animal Health can formulate these DNA plasmids together to rapidly develop a universal influenza vaccine potentially targeting all important strains. The resulting vaccine could target seasonal as well as pandemic-potential influenza strains such as avian influenza and swine flu, which has already been designated pandemic status. Significantly, being based on a common set of antigens derived from a broad range of flu strains, such a universal vaccine would have the potential to provide greater protection against evolving, unmatched flu strains in multiple species.

In a continuation of this study, Inovio investigators tested the immune sera for responses against a virus isolated from the current circulating strain of swine origin influenza A/H1N1 (Swine A/Mexico/InDRE4487/2009). All the animals immunized with the SynCon™ H1N1 vaccine developed HI titers exceeding the 1:40 level commonly associated with protective immunity.

In a second study, the investigators immunized mice with the NP and m2E components of the vaccine and challenged these animals with a second related strain also isolated from the current circulating influenza A/H1N1 (A/Canada/AB/RV1532/2009). While all mice showed effects of virus challenge as judged by significant weight loss, the vaccinated mice recovered from virus infection-induced morbidity significantly faster compared to the non-immunized control animals.

In a previous study, the Inovio team demonstrated that mice immunized with Inovio's SynCon™ H1N1 DNA vaccine provided 100% protection in a lethal challenge study against an unmatched H1N1 virus that caused the 1918 Spanish flu, which killed over 40 million people worldwide.

The challenge of current seasonal influenza vaccines is they are not effective against new strains that emerge, like the present swine origin influenza A/H1N1. The CDC reported low human prevaccination response rates and cross-reactivity to swine origin influenza (A/California/04/2009), suggesting that current H1N1 seasonal flu vaccines were likely to be ineffective against the new 2009 A/H1N1 strains. Similarly, the USDA recently reported there was limited cross-reactivity against the new 2009 A/H1N1 virus in pig herds vaccinated with existing swine influenza vaccines.

Dr. J. Joseph Kim, Inovio's CEO, said, "The latest data further underscores the potential of the SynCon™ technology to create vaccines capable of protecting against emerging pandemic influenza viruses. Our SynCon™ influenza vaccines were developed prior to the emergence of the current swine flu strains and have yielded strong protective responses in animal models against a variety of unmatched influenza strains. This is an advantage for our universal flu program over conventional influenza vaccines, which are strain-specific. Inovio, along with its collaborators, is amongst the first groups to report on the successful protection of vaccinated animals against a virus challenge with the 2009 influenza A/H1N1 virus. We are also one of the first groups to report on preclinical results regarding this virus using a large-animal model like pigs, a more natural host for the current influenza pandemic."

Inovio's novel SynCon™ technology enables the company to design DNA-based vaccines with the potential to protect against unmatched sub-types and strains of pathogens and provides the opportunity to have vaccines on hand against new strains that perpetually emerge, as in the case of influenza. Inovio has created SynCon™ DNA vaccines based on influenza HA, NA, and NP proteins from strains H1N1, H2N2, H3N2, and H5N1, which make up the majority of seasonal and pandemic influenza. Resulting vaccines could target seasonal as well as pandemic-potential influenza strains such as avian influenza and swine-origin flu, which has already been designated pandemic status. Significantly, being based on a common set of antigens derived from a broad range of flu strains, a universal vaccine would have the potential to provide greater protection against new, unmatched flu strains.

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DNA Vaccines

DNA-based vaccines and therapeutics deliver the immunogen or the therapeutic protein in the form of plasmid DNA encoding the protein of interest. The body then produces the protein of interest and elicits the appropriate immunologic response. Vaccination with DNA has multiple potential advantages over the present vaccine technology for a variety of infectious diseases. DNA vaccines are easier to manufacture, can be stored at room temperature, and have less safety concerns when delivered to the patient. Furthermore, when compared to viral vectors, they have the potential to more easily combine multiple antigens in one injection that would provide protection against multiple diseases or multiple targets from the same organism.

Over the last two decades, DNA vaccines have become a potent means of providing immune responses or protective immunity against viruses, bacteria and parasites in many species from fish to primates, including humans. DNA vaccines, comprised of plasmid DNA encoding proteins from pathogens, allergens, and tumors, are being evaluated as prophylactic vaccines and therapeutic treatments for infectious diseases, allergies and cancer. The use of DNA as a means of vaccination offers advantage in protective efficacy, cross-strain applicability, development speed and manufacturing cost over conventional vaccines. DNA vaccines are known to be particularly effective in inducing killer T-cell responses which are critical to fighting infections.

VGX Animal Health plans to exploit the early progress in human influenza vaccines in their development program for DNA vaccines to:
		Traditional Swine Influenza Virus
		Universal Influenza Viral Vaccines
		Porcine Reproductive and Respiratory Syndrome Virus
		Other

Work has begun on SynCon™ vaccines for these three diseases, and data coming out of these studies should lay the foundation for USDA license applications in 2010-2011.